Butyrate interacts with the effects of 2'FL and 3FL to modulate in vitro ovalbumin-induced immune activation, and 2'FL lowers mucosal mast cell activation in a preclinical model for hen's egg allergy.

Autor:	Zuurveld M; Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands., Diks MAP; Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands., Kiliaan PCJ; Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands., Garssen J; Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands.; Danone Nutricia Research B.V, Utrecht, Netherlands., Folkerts G; Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands., Van't Land B; Danone Nutricia Research B.V, Utrecht, Netherlands.; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands., Willemsen LEM; Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands.
Jazyk:	angličtina
Zdroj:	Frontiers in nutrition [Front Nutr] 2023 Dec 19; Vol. 10, pp. 1305833. Date of Electronic Publication: 2023 Dec 19 (Print Publication: 2023).
DOI:	10.3389/fnut.2023.1305833
Abstrakt:	Background: Early life provides a window of opportunity to prevent allergic diseases. With a prevalence of 0.5-2% in infants, hen's egg allergy is one of the most common food allergies. The immunomodulatory effects of human milk oligosaccharides (HMOs), 2'-fucosyllactose (2'FL), and 3-fucosyllactose (3FL) were studied in an in vitro mucosal immune model and an in vivo murine model for hen's egg (ovalbumin) allergy. Methods: Intestinal epithelial cell (IEC)/dendritic cell (DC) and DC/T cell cocultures were used to expose IECs to ovalbumin (OVA) in an in vitro mucosal immune model. The effects of epithelial pre-incubation with 0.1% 2'FL or 3FL and/or 0.5 mM butyrate were studied. Three- to four-weeks-old female C3H/HeOuJ mice were fed AIN93G diets containing 0.1-0.5% 2'FL or 3FL 2 weeks before and during OVA sensitization and challenge. Allergic symptoms and systemic and local immune parameters were assessed. Results: Exposing IECs to butyrate in vitro left the IEC/DC/T cell cross-talk unaffected, while 2'FL and 3FL showed differential immunomodulatory effects. In 3FL exposed IEC-DC-T cells, the secretion of IFNγ and IL10 was enhanced. This was observed upon pre-incubation of IECs with 2'FL and butyrate as well, but not 2'FL alone. The presence of butyrate did not affect OVA activation, but when combined with 3FL, an increase in IL6 release from DCs was observed ( p  < 0.001). OVA allergic mice receiving 0.5% 3FL diet had a lower %Th2 cells in MLNs, but the humoral response was unaltered compared to control mice. OVA-allergic mice receiving 0.1 or 0.5% 2'FL diets had lower serum levels of OVA-IgG2a ( p  < 0.05) or the mast cell marker mMCP1, in association with increased concentration of cecal short-chain fatty acids (SCFAs) ( p  < 0.05). Conclusion: In vitro butyrate exposure promotes the development of a downstream type 1 and regulatory response observed after 2'FL exposure. 2'FL and 3FL differentially modulate ovalbumin-induced mucosal inflammation predominantly independent of butyrate. Mice receiving dietary 3FL during ovalbumin sensitization and challenge had lowered Th2 activation while the frequency of Treg cells was enhanced. By contrast, 2'FL improved the humoral immune response and suppressed mast cell activation in association with increased SCFAs production in the murine model for hen's egg allergy. Competing Interests: JG and BL are partially employed by Danone Nutricia Research B.V. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2023 Zuurveld, Diks, Kiliaan, Garssen, Folkerts, van’t Land and Willemsen.)
Databáze:	MEDLINE
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